Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Abstract

Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development. Recommendations New or revised recommendations include the following. Regarding first-line treatment for patients with non-squamous cell carcinoma or squamous cell carcinoma (without positive markers, eg, EGFR/ALK /ROS1), if the patient has high programmed death ligand 1 (PD-L1) expression, pembrolizumab should be used alone; if the patient has low PD-L1 expression, clinicians should offer standard chemotherapy. All other clinical scenarios follow 2015 recommendations. Regarding second-line treatment in patients who received first-line chemotherapy, without prior immune checkpoint therapy, if NSCLC tumor is positive for PD-L1 expression, clinicians should use single-agent nivolumab, pembrolizumab, or atezolizumab; if tumor has negative or unknown PD-L1 expression, clinicians should use nivolumab or atezolizumab. All immune checkpoint therapy is recommended alone plus in the absence of contraindications. For patients who received a prior first-line immune checkpoint inhibitor, clinicians should offer standard chemotherapy. For patients who cannot receive immune checkpoint inhibitor after chemotherapy, docetaxel is recommended; in patients with nonsquamous NSCLC, pemetrexed is recommended. In patients with a sensitizing EGFR mutation, disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mutation, then chemotherapy is recommended. Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.

Complications and Economic Burden Associated with Obtaining Tissue for Diagnosis and Molecular Analysis in Patients with Non-Small Cell Lung Cancer (NSCLC) in the US (Preprint)

“…Osimertinib is a third-generation, EGFR-TKI that potently and selectively inhibits both EGFR sensitizing and EGFR T790M resistance mutations [5,17,18]. Based on positive results from the AURA trial program and FLAURA first-line study, osimertinib is recommended in the US as a first-line treatment option for patients with EGFR mutation-positive advanced NSCLC and as a second-line treatment for patients with T790M-positive NSCLC following disease progression on a first-line EGFR-TKI therapy (erlotinib, gefitinib, or afatinib) [12,19]. Thus, EGFR mutation testing at diagnosis and T790M testing following progression on an EGFR-TKI are now recommended in clinical guidelines and are standard of care in clinical practice [3].…”

“…When considering the use of targeted therapies for anaplastic lymphoma kinase (ALK)-rearranged and epidermal growth factor receptor (EGFR) mutation-positive NSCLC, tumor biopsy or blood-based testing is required to confirm tumor mutation status and assist with appropriate patient selection [3,12,13]. With the increase in availability of additional mutation-and translocation-based targeted therapies and immunotherapies, molecular and immune micro-environment testing at diagnosis and progression have become increasingly important to understand molecular mechanisms of resistance and for the effective management of NSCLC.…”

Can radiotherapy potentiate the effectiveness of immune checkpoint inhibitors in lung cancer?

“…These agents have produced durable clinical responses and antitumor activity in Phase I trials, leading to subsequent randomized Phase II and III trials that demonstrated significant improvements in overall survival when compared with cytotoxic chemotherapy alone [12][13][14][15][16]. These studies have established PD-1/PD-L1 pathway blockade as a powerful new line of therapy for patients with advanced NSCLC following progression after platinum-based therapy [9,11]. Despite unprecedented improvements in clinical outcomes, less than 20% of patients respond to anti-PD-1/PD-L1 agents, necessitating strategies that explore combined treatment modalities in order to extend the benefits of immune checkpoint blockade to a broader patient population.…”

“…Immune checkpoint inhibitors of the PD-1/PD-L1 pathway have emerged as a promising new therapeutic strategy [8][9][10][11]. These agents have produced durable clinical responses and antitumor activity in Phase I trials, leading to subsequent randomized Phase II and III trials that demonstrated significant improvements in overall survival when compared with cytotoxic chemotherapy alone [12][13][14][15][16].…”

“…By activating the immune system to recognize and eliminate cancer, immune checkpoint blockade has the potential to elicit durable responses and augment survival outcomes for a subset of patients [1,2]. In addition, the ability of radiotherapy to induce an immunogenic response and neutralize the immune-suppressive effects of the tumor microenvironment, uniquely positions it as a synergistic tool at the center of emerging multimodal therapies utilizing immune checkpoint blockade [3][4][5][6][7].Immune checkpoint inhibitors of the PD-1/PD-L1 pathway have emerged as a promising new therapeutic strategy [8][9][10][11]. These agents have produced durable clinical responses and antitumor activity in Phase I trials, leading to subsequent randomized Phase II and III trials that demonstrated significant improvements in overall survival when compared with cytotoxic chemotherapy alone [12][13][14][15][16].…”